{rfName}
No

Indexed in

License and Use

Icono OpenAccess

Citations

10

Altmetrics

Analysis of institutional authors

Herrera SAuthorRoca IAuthorVila JAuthorCasals-Pascual CAuthor

Share

January 31, 2025
Publications
>
Article
No

Novel PiuC, PirA, and PiuA mutations leading to in vivo cefiderocol resistance progression in IMP-16- and KPC-2-producing Pseudomonas aeruginosa from a leukemic patient.

Publicated to: Microbiology Spectrum. 13 (3): e0192824- - 2025-01-28 13(3), DOI: 10.1128/spectrum.01928-24

Authors:

Viñes J; Herrera S; Vergara A; Roca I; Vila J; Aiello TF; Martínez JA; del Río A; Lopera C; Garcia-Vidal C; Casals-Pascual C; Soriano À; Pitart C
[+]

Affiliations

Departament de Malalties Infeccioses, Hospital Clínic de Barcelona, Barcelona, Spain. - Author
Servei de Microbiologia i Parasitologia-CDB, Hospital Clínic de Barcelona, Barcelona, Spain. - Author

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen capable of causing severe infections in immunocompromised individuals, who often require prolonged antibiotic therapy. The emergence of carbapenemase-producing P. aeruginosa has further complicated the management of nosocomial infections, limiting therapeutic options. Cefiderocol has recently emerged as a promising antipseudomonal agent, using the bacterial iron transport system to gain entry into the cell; however, there have been reports of P. aeruginosa resistant to cefiderocol. We describe the in vivo cefiderocol resistance progression of four consecutive P. aeruginosa isolates from one patient with T-cell acute lymphoblastic leukemia. Analysis of potential genes involved in cefiderocol transport resulted in three genes mutated in two resistant isolates. One isolate presented a S116F substitution in PiuC, and the other presented a deletion of 29 amino acids in the signal peptide of PiuA and a STOP substitution in PirA, resulting in the deletion of a piece of the channel. These mutations increased 24- and 64-folds the cefiderocol minimum inhibitory concentration, respectively. The mutations in the aforementioned genes may directly impact siderophore internalization, thereby contributing to an elevation in the MIC of the antibiotic. Carbapenem-resistant Pseudomonas aeruginosa poses a significant challenge due to its broad antibiotic resistance. Cefiderocol is a novel antibiotic aimed at combating infections caused by such organisms. However, if these pathogens develop resistance to this new drug, it hinders treatment efficacy and options. Therefore, it is crucial to identify and describe mutations in the genes involved in the uptake of cefiderocol to find better treatment strategies for patients infected with multidrug-resistant P. aeruginosa.
[+]

Keywords

Anti-bacterial agentsAntiinfective agentAvibactam plus ceftazidimeAztreonamBacterial proteinBacterial proteinsBeta lactamaseBeta-lactamasesCarbapenem-resistantCarbapenemase 2CefiderocolCephalosporinsCyclophosphamideCytarabineDexamethasoneDoxorubicinDrug effectDrug resistance, multiple, bacterialDrug therapyGeneticsHumansHypertensive factorImipenemase 16In vivo studyInduction chemotherapyInotuzumab ozogamicinInternalization (cell)Invasive ventilationIsavuconazoleLeukemiaLevofloxacinLung consolidationMaleMatrix assisted laser desorption ionization time of flight mass spectrometryMercaptopurineMetabolismMicrobial sensitivity testMicrobial sensitivity testsMicrobiologyMinimal residual diseaseMinimum inhibitory concentrationMitoxantroneMultidrug resistanceMultidrug resistant pseudomonas aeruginosaMutationNanopore sequencingNeutropenic enterocolitisNonhumanNonsense mutationNorovirus infectionNuclear magnetic resonance imagingNucleotide sequenceOxford nanoporePiperacillin plus tazobactamPiraPira proteinPiuaPiua proteinPiucPiuc proteinPseudomonas aeruginosaPseudomonas infectionPseudomonas infectionsQuality controlRectal swabRespiratory tract diseaseRituximabSecond-line treatmentSeptic shockSiderophoreStenotrophomonas maltophiliaSwabbingT cell acute lymphoblastic leukemiaTeicoplaninThorax radiographyTomographyUnclassified drugUrine samplingVincristineWound swab

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Microbiology Spectrum due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2025, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Ecology.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-04-16:

  • Scopus: 9
[+]

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-16:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 10.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 10 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
[+]

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Viñes J) and Last Author (Pitart C).

[+]